Modeling and analysis of the latent period of osteosarcomas induced by incorporated Pu-239: The role of immune responses

This paper considers the utility of a stochastic model of carcinogenesis, p roposed earlier by Yakovlev and Polig, ill quantitative analysis of tile in cidence of radiation-induced osteosarcomas in beagles injected with various amounts Pu-239. The original version of tile model failed to provide a goo d fit to our experimental data. Tile model has been generalized by incorpor ating a simple mechanism of lesion elimination, which is likely to be media ted by the immune system. Two versions of tile model were developed: the fi rst version (Model 1) assumed malignant cells to be a target for the immune attack, while in Model 2 initiated cells were assumed to be such a target. Model 2 was rejected by the likelihood ratio test, thereby indicating that the competing model provides rt more plausible explanation of the experime ntal data. Since in experiments with incorporated radionuclides the dose ra te varies with time, dose-rate effects cannot be observed directly, and one must rely on mathematical models. The results of our numerical experiments show that, depending on the time of observation, both the direct and the i nverse dose-rate effects may manifest themselves even at a fixed total dose level. (C) 2001 Elsevier Science Ltd. All rights reserved.